[⁶⁸Ga]Ga-NOTA-T4 ImmunoPET imaging for evaluating TROP2 expression in patients with solid tumors

Gallium-68 (⁶⁸Ga)-labeled [⁶⁸Ga]Ga-NOTA-T4 immuno-positron emission tomography (immunoPET) holds great promise as a non-invasive technique for visualizing the expression of trophoblast cell-surface antigen 2 (TROP2). This approach may potentially assist in making clinical decisions regarding TROP2-targeted therapies. The present study aims to evaluate the utility of [⁶⁸Ga]Ga-NOTA-T4 PET/CT in detecting TROP2 expression levels, diagnosing primary tumors and metastatic lesions. Additionally, it conducts a direct comparison with fluorine-18-labeled fluorodeoxyglucose ([¹⁸F]FDG) PET/CT.

Participants with solid tumors who underwent [⁶⁸Ga]Ga-NOTA-T4 PET/CT scans were prospectively recruited between October 2023 and August 2024. A subset of these participants also received [¹⁸F]FDG PET/CT. The uptake in physiological organs was quantified using the mean standardized uptake value (SUVmean). Positive lesions were identified through visual assessments and further quantified using the maximum standardized uptake value (SUVmax) and the target-to-background ratio (TBR). The TBR was calculated by dividing the SUVmax of the lesion by the SUVmean of the background, where the brain background was used for cerebral lesions and the blood pool for other lesions. TROP2 expression levels were evaluated via immunohistochemical (IHC) tumor proportion score (TPS). Biodistribution, lesion detectability, and the correlation with TROP2 were analyzed for both tracers using appropriate statistical methods.

A total of 26 patients (mean age: 63 ± 10 years; 13 females) were included in the study. [⁶⁸Ga]Ga-NOTA-T4 demonstrated high uptake in the kidneys, pancreas, thyroid, and submaxillary gland, while showing low uptake in the brain, muscle, and bone. Both tracers successfully detected all 19 primary/recurrent tumors. However, [⁶⁸Ga]Ga-NOTA-T4 presented lower SUVmax and TBR compared to [¹⁸F]FDG (1.93 [1.36, 2.58] vs. 11.37 [6.45, 13.15], P < 0.001; 2.83 [2.17, 3.74] vs. 6.95 [5.24, 11.27], P = 0.03, respectively). [⁶⁸Ga]Ga-NOTA-T4 identified fewer suspected metastases but detected two brain metastases that were missed by [¹⁸F]FDG. TROP2 TPS was positively correlated with [⁶⁸Ga]Ga-NOTA-T4 SUVmax (r = 0.85, P = 0.002) and TBR (r = 0.66, P = 0.030), while no significant correlation was observed for [¹⁸F]FDG.

[⁶⁸Ga]Ga-NOTA-T4 PET/CT emerges as a promising non-invasive tool for assessing TROP2 expression levels and diagnosing solid tumors. In certain specific cases, it exhibits potential advantages over [¹⁸F]FDG.